Field
This invention relates to a dosage form that is a capsule containing one or more tablets of 5-aminosalicylic acid or a salt thereof as an active ingredient and each of the one or more tablets being enterically coated. Simple encapsulation can be employed to achieve benefits in handling. It has been unexpectedly discovered that a capsule shell having a relatively low moisture content provides a dosage form that inhibits the formation of degradants within the enterically coated tablets contained within the capsule shell during the storage of the dosage form.
Related Background Art
The use of 5-aminosalicylic acid (mesalazine, mesalamine or 5-ASA) for the treatment of ulcerative colitis or Crohn's disease of the colon is well known. U.S. Pat. Nos. 5,541,170 and 5,541,171 describe dosage forms of actives, such as 5-aminosalicylic acid, that are enterically coated to facilitate delivery of the active ingredient to the colon. More specifically, a capsule dosage form containing 5-aminosalicylic acid with a gelatin capsule shell having a coating of EUDRAGIT S100 applied to the capsule shell, is exemplified. U.S. Pat. No. 6,893,662 describes dosage forms of actives, such as 5-aminosalicylic acid, having inner and outer polyacrylate coatings. None of these references discloses an enterically coated tablet of 5-aminosalicylic acid in a capsule.
It is known that 5-aminosalicylic acid dosage forms formulated with a reducing sugar, such as lactose, are subject to degradation, particularly when prepared using an aqueous wet granulation technique or subjected to high humidity. This degradation will produce a breakdown product (5-[2-formyl-5-(hydroxymethyl-1H-pyrrol-1-yl]-2-hydroxybenzoic acid (herein referred to as degradant B or deg B) that can limit shelf life and reduce the performance of the product. It has been surprisingly found that encapsulation of enterically coated tablets can enhance stability. U.S. Patent Application Publication No. 2010/0210605 teaches that such degradation may be reduced by providing a dosage form in a kit with a predetermined amount of desiccant. While the use of low moisture hydroxypropylmethyl cellulose (HPMC) capsules was known for use with capsule fills of water-sensitive actives (see HPMC Capsules: New Generation Drug Delivery Technology, Vol. 2, No. 2, March/April 2002), there was little expectation that the moisture content of a capsule would have a discernible effect on the stability of an enterically coated tablet of 5-aminosalicylic acid contained therein.